Biomedical subjects
R Yehuda
Publications and source records attributed to R Yehuda.
Relationships between hormonal profile and novelty seeking in combat-related posttraumatic stress disorder.
This study examines relationships between hormonal levels and novelty seeking in a group of 27 Vietnam veterans with combat-related posttraumatic stress disorder (PTSD). Novelty seeking in the veteran sample, measured by the Cloninger Tridimensional Personality Questionnaire (TPQ), was almost twice as high as previously published norms. A distinctive pattern of significant positive correlations was found between novelty seeking scores and serum total triiodothyronine (T3), free T3, the T3/free thyroxine (FT4) ratio, urinary norepinephrine and the norepinephrine/cortisol ratio, while a negative correlation was found between novelty seeking scores and urinary cortisol levels. The findings were confirmed by t test analyses of high vs low novelty seeking subgroups and do not appear to be related simply to the severity of PTSD. These preliminary findings indicate the need to include measures of characterological traits in psychoendocrine studies of PTSD and to investigate their possible usefulness in subtyping this disorder.
Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor mRNA expression in the luteal phase of the menstrual cycle.
We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal axis regulation in healthy women with no history of psychiatric illness by measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N = 23) and by measuring glucocorticoid receptor (type II) mRNA expression in lymphocytes using Northern blotting (N = 19). Both measures were performed in the early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone suppression of plasma cortisol was greater in the follicular phase of the menstrual cycle compared to the mid-luteal phase (p < .01). In addition, type II glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the follicular phase compared to the mid-luteal phase (p < .02). These results indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis is reduced in the mid-luteal phase of the menstrual cycle. Reduced feedback regulation of central stress response systems may play a role in generation of common premenstrual symptoms of irritability and dysphoria.
Individual differences in posttraumatic stress disorder symptom profiles in Holocaust survivors in concentration camps or in hiding.
Symptom patterns were compared between Holocaust survivors in concentration camp (n = 70) and those who were in "hiding" (n = 30) during the war. The impact of age at the time of the trauma, gender, and cumulative lifetime stress, and the effect of each of these variables controlling for the others, on posttraumatic stress disorder (PTSD) symptoms were also evaluated. A significant negative relationship between age at the time of the trauma and symptoms of psychogenic amnesia, hypervigilence and emotional detachment, and a positive correlation between age and intrusive thoughts, were observed. Cumulative lifetime stress was positively associated with symptoms of avoidance. The study provides the first empirical data regarding the factors that potentially explain individual differences in PTSD symptom patterns in Holocaust survivors.
Alexithymia in Holocaust survivors with and without PTSD.
Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale-Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.
Prolactin response to low-dose dexamethasone challenge in combat-exposed veterans with and without posttraumatic stress disorder and normal controls.
The prolactin and cortisol responses to dexamethasone (0.5 mg) were studied in combat veterans with (n = 18) and without (n = 12) posttraumatic stress disorder (PTSD) and normal controls (n = 18). Both veteran groups demonstrated greater prolactin suppression than the normals. In contrast, only veterans with PTSD showed an enhanced cortisol suppression in response to dexamethasone. These findings suggest that the prolactin response to dexamethasone may reflect a feature of combat exposure rather than PTSD per se.
Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.
The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period of bed rest. Raw cortisol data were modeled using standard and multioscillator cosinor models to determine the best fitting functions for circadian, hemicircadian, and ultradian components of cortisol release. PTSD subjects had substantially lower cortisol levels, and displayed a pattern of cortisol release that was better modeled by circadian rhythm. PTSD subjects also showed a greater circadian signal-to-noise ratio than the other groups. In contrast, depressed patients displayed a less-rhythmic, more chaotic pattern of cortisol release. The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.
Increased pituitary activation following metyrapone administration in post-traumatic stress disorder.
Our previous findings have demonstrated that individuals with post-traumatic stress disorder (PTSD) show lower basal cortisol levels, a larger number of lymphocyte glucocorticoid receptors, and an enhanced suppression of cortisol following the administration of dexamethasone compared to normals and patients with major depression. We have previously suggested that these alterations reflect an enhanced negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD. However, in the absence of direct knowledge of pituitary capability in this disorder, it has been equally likely that the alterations observed reflected either pituitary or adrenal insufficiency. In the present study, we examined ACTH release from the pituitary gland in PTSD following the administration of metyrapone. Metyrapone resulted in a significantly greater increase of ACTH and 11-deoxycortisol in combat veterans with PTSD (n = 11) compared with normal male volunteers (n = 8). When seen in the context of other abnormalities observed in PTSD, the present demonstration of increased pituitary activity in the absence of negative feedback provides unequivocal support for the hypothesis of enhanced negative feedback.
Basal cortisol, dexamethasone suppression of cortisol, and MHPG in adolescents after the 1988 earthquake in Armenia.
OBJECTIVE: This study evaluated basal salivary cortisol, 3-methoxy-4-hydroxyphenylglycol (MHPG), and cortisol suppression following dexamethasone administration in adolescents exposed to two levels of earthquake-related trauma. METHOD: Five years after the 1988 earthquake, saliva samples were obtained from 37 adolescents from two cities in Armenia at different distances from the epicenter. Baseline saliva samples were obtained at 8:00 a.m., 4:00 p.m., and 11:00 p.m., following which 0.5 mg of dexamethasone was administered. Nine and 17 hours later, saliva samples were again obtained. Subjects were evaluated for posttraumatic stress and depressive reactions through use of self-report instruments. RESULTS: Significantly lower mean baseline 8:00 a.m. cortisol levels and greater day 24:00 p.m. cortisol suppression following dexamethasone were observed in the more symptomatic adolescents living in the city closer to the epicenter. Of the three symptom categories of posttraumatic stress disorder (PTSD), only intrusion (category B) symptoms were significantly correlated with basal morning cortisol levels and percent suppression by dexamethasone. The more highly exposed adolescents also exhibited a more rapid decline in MHPG levels over the course of day 1. CONCLUSIONS: The findings indicate that chronic posttraumatic stress reactions among adolescents exposed to catastrophic disaster are associated with hypothalamic-pituitary-adrenal (HPA) axis alterations. The findings are congruent with those previously described in adults with chronic PTSD. Persistent intrusion (category B) symptoms may constitute continued episodes of distress and evoke repeated physiological stress responses, which, over time, alter HPA axis function. The MHPG findings suggest that there may be diurnal changes associated with severity of posttraumatic stress symptoms.
Dissociation in aging Holocaust survivors.
OBJECTIVE: This study explored relationships among dissociation, trauma, and posttraumatic stress disorder (PTSD) in elderly Holocaust survivors with and without PTSD and in a demographically comparable group of nontraumatized subjects. METHOD: Holocaust survivors with PTSD (N = 35) and without PTSD (N = 25) who had been recruited from the community and a comparison group (N = 16) were studied. Dissociation was evaluated with the Dissociative Experiences Scale. Past cumulative trauma and recent stress were evaluated with the Antonovsky Life Crises Scale and the Elderly Care Research Center Recent Life Events Scale, respectively. PTSD symptoms were assessed with the Clinician-Administered PTSD Scale. RESULTS: The Holocaust survivors with PTSD showed significantly higher levels of current dissociative experiences than did the other groups. However, the extent of dissociation was substantially less than that which has been observed in other trauma survivors with PTSD. Dissociative Experiences Scale scores were significantly associated with PTSD symptom severity, but the relation between Dissociative Experiences Scale scores and exposure to trauma was not significant. CONCLUSIONS: Possible explanations for this finding include the age of the survivors, the length of time since the traumatic event, and possible unique features of the Holocaust survivor population. Nevertheless, the findings call into question the current notion that PTSD and dissociative experiences represent the same phenomenon. The findings suggest that the relationships among dissociation, trauma, and PTSD can be further clarified by longitudinal studies of trauma survivors.
Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients.
This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age-range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls. The time course of diurnal heart rate also differed in acutely depressed patients from controls: acutely depressed patients started higher and converged by midday to normal levels. These diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression.
Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder.
BACKGROUND: Our previous studies have suggested that combat veterans with posttraumatic stress disorder (PTSD) have alterations in hypothalamic-pituitary-adrenal axis functioning that are different from the well-documented biological changes observed in major depressive disorder and following exposure to stress. METHODS: In the present study, we examined cortisol and lymphocyte glucocorticoid receptor number before and after the administration of 0.50 and 0.25 mg of dexamethasone in 14 combat veterans with PTSD, 12 combat veterans without PTSD, and 14 nonpsychiatric healthy men. All subjects were medication free at the time of testing and none met diagnostic criteria for major depression or substance dependence. RESULTS: Combat veterans with PTSD suppressed cortisol to a greater extent than did combat veterans without PTSD and normal controls in response to both doses of dexamethasone. Differences in cortisol suppression could not be attributed to substance dependence history or differences in dexamethasone bioavailability. Combat veterans with PTSD showed a larger number of baseline glucocorticoid receptors compared with normal men. Combat veterans without PTSD also had a larger number of baseline glucocorticoid receptors compared with normal men and in fact were comparable to combat veterans with PTSD on this measure. However, only veterans with PTSD showed a decrease in lymphocyte glucocorticoid receptor number following dexamethasone administration. CONCLUSION: The data support the hypothesis of an enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal axis in PTSD.
Learning and memory in combat veterans with posttraumatic stress disorder.
OBJECTIVE: The authors investigated a broad range of memory functions for stimuli unrelated to trauma to determine whether symptoms such as intrusive memories might reflect an underlying cognitive deficit unrelated to the psychological content of the traumatic memory in patients with posttraumatic stress disorder (PTSD). METHOD: The authors measured the intellectual functioning of 20 male combat veterans with PTSD and 12 normal comparison subjects using the WAIS and evaluated them for performance on memory using the California Verbal Learning Test. RESULTS: Veterans with PTSD showed normal abilities in the functions of initial attention, immediate memory, cumulative learning, and active interference from previous learning. However, these veterans showed a circumscribed cognitive deficit, manifested by the presence of substantial retroactive interference and revealed by a significant decrement in retention following exposure to an intervening word list. CONCLUSIONS: The data suggest that patients with PTSD may have fairly specific deficits in the monitoring and regulation of memory information.
Effect of previous trauma on acute plasma cortisol level following rape.
OBJECTIVE: The authors examined the relationships among history of previous assault, severity of rape, acute plasma cortisol level after rape, and development of rape-related post-traumatic stress disorder (PTSD). METHOD: Blood samples were drawn from 37 adult female rape victims within 51 hours after they had been raped. The subjects were assessed for history of previous assault and for the presence of PTSD 17-157 days (mean = 90 days) after the rape. RESULTS: Women with a history of previous assault had a lower mean acute cortisol level after the rape but a higher probability of subsequently developing PTSD. A significant interaction between history of previous assault and the severity of the index rape was observed: only women who had never been assaulted before had higher cortisol levels following high-severity rapes (those which included injury or multiple types of penetration) than low-severity rapes. CONCLUSIONS: The authors conclude that previous traumatization may attenuate the acute cortisol response to trauma.
Conflict between current knowledge about posttraumatic stress disorder and its original conceptual basis.
OBJECTIVE: The author's goal was to explore the historical, political, and social forces that have played a major role in the acceptance of the idea of trauma as a cause of the specific symptoms of posttraumatic stress disorder (PTSD) and to discuss the impact that current research findings have had on some of the initial conceptualizations of the disorder. METHOD: The conceptual origins of PTSD are described, and the literature on the prevalence, longitudinal course, phenomenology, and neurobiology of PTSD is reviewed. RESULTS: Paradoxically, there are a series of findings that support the idea that PTSD is a distinct diagnostic entity, but these are different from those originally developed from psychosocial theory and stress research. CONCLUSIONS: PTSD has been a controversial diagnosis and is again at a vulnerable point. It is imperative that the field address how current findings challenge the original conceptualizations of this disorder so that the next generation of conceptual issues can be formulated.
Impact of cumulative lifetime trauma and recent stress on current posttraumatic stress disorder symptoms in holocaust survivors.
OBJECTIVE: The purpose of this study was to examine the relationships among cumulative lifetime trauma, recent stressful events, and presence and severity of current posttraumatic stress disorder (PTSD) symptoms in Holocaust survivors and nonexposed comparison subjects. METHOD: Lifetime trauma, recent stressful events, and presence and severity of PTSD were assessed in Holocaust survivors (N=72) and comparison subjects ( N=19). RESULTS: Survivors with PTSD (N =40) reported significantly greater cumulative trauma and recent stress than survivors without PTSD (N=32) and comparison subjects. Severity of PTSD symptoms, cumulative trauma, and recent stress were significantly associated. CONCLUSIONS: The presence and severity of current PTSD were related to having experienced stressful events in addition to the Holocaust.
Lack of significant cortisol and growth hormone changes in Israeli civilians during the Gulf War.
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Psychological dimensions of depression in borderline personality disorder.
OBJECTIVE: The authors' goal was to test empirically a commonly held assumption that the depression in borderline personality disorder is primarily anaclitic. METHOD: The Depressive Experiences Questionnaire and the Hamilton Rating Scale for Depression were administered to 26 patients with borderline personality disorder (16 of whom were depressed) and 12 depressed patients without borderline personality disorder. RESULTS: Patients with borderline personality disorder showed more self-criticism but did not endorse more anaclitic items than depressed patients without borderline personality disorder. CONCLUSIONS: These findings suggest that self-criticism is an underemphasized characteristic of depression in borderline personality disorder.